BS2550 - Neuronal and Cellular Signalling Lecture 5 The Role of Calcium in the Nervous System Calcium has multiple roles in the nervous system. Soluble calcium ions can act as a charge carrier (cardiac AP), these are free moving molecules. It can also act as a signalling molecule (energy output, cellular metabolism). Most of the intracellular calcium is buffered (bound to some other molecules) and the concentration of free calcium is very low which creates a large electrochemical gradient. In the insoluble form, it is the major structural constituent of bones and teeth. Nernst Potential Electrochemical equilibrium results in no net movement of ions across the membrane. When the charge changes it changes the electrochemical gradient as some of the ions get pulled from one side or the other. If a membrane were selectively permeable to potassium ions alone, its membrane potential would be at Ex (equilibrium potential of potassium). To calculate the Nernst potential for a cation the following equation can be used: RT log [X]out [X]in Ex= zF Where Z is the number of electrons (valency), F is Faraday's constant (96485 C mol-1), R is the gas constant (8.31446261815324 J.K-1.mol-1), and T is the temperature in Cell 1 Cell 2 Kelvin. For an anion, the concentration in is 50 +50 mV 0 divided by the concentration out. -25 mV (mV) presynaptic potential -70 At the NMJ, calcium ions facilitate action potential triggered neurotransmitter release from the presynaptic cell. 0 presynaptic Ca2' current (HA) -3 Low extracellular calcium ions concentration reduces the likelihood of EPP generation in the postsynaptic cell and they also serves as a second messenger during neurotransmitter release. -6 A 'tail' Ca2+ current -9 0 -25 postsynaptic current (HA) -50 -75 time - 5 ms Calcium entry into the presynaptic terminal occurs when the sodium voltage gated channels and voltage steps are applied to both cells.
In cell one, there is moderate depolarization which results in a presynaptic current followed by a postsynaptic EPP. In cell two there is a strong depolarization which does not trigger a presynaptic calcium ion current or a postsynaptic EPP. For neurotransmitter release there needs to be sufficient calcium, calcium is necessary for this. The Mechanism for Neurotransmitter Release - Upon propagation of an action potential into the nerve terminal, there is an influx of Ca2+ through voltage-activated Ca2+ channels. - This transiently increases the local Ca2+ concentration at the presynaptic active zone, triggering the fusion of docked synaptic vesicles to the presynaptic membrane. Ca2+ then triggers neurotransmitter release within a few hundred microseconds by activating synaptotagmins Ca2+. - Synaptotagmins bind Ca2+ via two C2-domains and transduce the Ca2+ signal into a nanomechanical activation of the membrane fusion machinerytt this activation is mediated by the Ca2+-dependent interaction of the synaptotagmin C2-domains with phospholipids and SNARE proteins. - In triggering exocytosis, synaptotagmins do not act alone, but require an obligatory cofactor called complexin, a small protein that binds to SNARE complexes and simultaneously activates and clamps the SNARE complexes, thereby positioning the